Related Experiment Video

Updated: Dec 20, 2025

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis
09:58

Mapping the Structure-Function Relationships of Disordered Oncogenic Transcription Factors Using Transcriptomic Analysis

Published on: June 27, 2020

3.0K

MDM2's dual mRNA binding domains co-ordinate its oncogenic and tumour suppressor activities

Sivakumar Vadivel Gnanasundram1, Laurence Malbert-Colas1, Sa Chen2

  • 1Inserm UMRS1131, Institut de Génétique Moléculaire, Université Paris 7, Hôpital St. Louis, F-75010 Paris, France.

Nucleic Acids Research
|May 27, 2020
PubMed

Insights

Epstein-Barr virus (EBV) protein EBNA1 causes translation stress, activating PI3Kδ and MDM2. This promotes E2F1 translation, impacting cell growth. MDM2

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Virology

Background:

  • Cell growth depends on protein synthesis; oncogenic pathways stimulate proliferation and ribosome biogenesis.
  • Cellular responses to mRNA translation dysfunction and their impact on growth regulation are not fully understood.
  • Epstein-Barr virus (EBV) protein EBNA1 induces mRNA translation stress, activating PI3Kδ.

Purpose of the Study:

  • To investigate how cells respond to mRNA translation stress induced by EBV's EBNA1.
  • To elucidate the role of MDM2 in regulating E2F1 translation under stress conditions.
  • To understand how MDM2 domains selectively bind mRNAs to control cell growth.

Main Methods:

  • Investigated the mechanism of EBNA1-induced mRNA translation stress.
  • Analyzed MDM2 binding to E2F1 mRNA and its regulation by phosphorylation and domains.
  • Studied the interaction of p14Arf with MDM2 and its effect on p53 and E2F1 mRNA binding.

Main Results:

  • EBNA1 activates PI3Kδ, stabilizing MDM2 and promoting E2F1 translation.
  • MDM2's serine 166 regulates E2F1 mRNA binding; deletion of the RING domain causes constitutive binding.
  • DNA damage-induced p53 phosphorylation prevents E2F1 mRNA binding, while p14Arf inhibits MDM2-E2F1 interaction.

Conclusions:

  • MDM2 utilizes distinct domains to bind specific mRNAs, regulating cell growth in response to cellular conditions.
  • p14Arf coordinates MDM2 activity towards both p53 and E2F1.
  • EBV's EBNA1 targets the E2F1 and MDM2-p53 pathways via translation stress to manipulate cell growth.

More Related Videos

CRISPR Gene Editing Tool for MicroRNA Cluster Network Analysis10:40

CRISPR Gene Editing Tool for MicroRNA Cluster Network Analysis

Published on: April 25, 2022

2.7K
Desthiobiotin-Streptavidin-Affinity Mediated Purification of RNA-Interacting Proteins in Mesothelioma Cells11:11

Desthiobiotin-Streptavidin-Affinity Mediated Purification of RNA-Interacting Proteins in Mesothelioma Cells

Published on: April 25, 2018

8.5K

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.0K
Master Transcription Regulators02:23

Master Transcription Regulators

Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.6K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
3.6K
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After...
23.7K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
7.1K
Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

2.4K